Insulin…an Undeserved Bad Reputation

I feel sorry for insulin. Insulin has been bullied and beaten up. It has been cast as an evil hormone that should be shunned. However, insulin doesn't deserve the treatment it has received.

Insulin: A Primer

Insulin is a hormone that regulates the levels of sugar in your blood. When you eat a meal, the carbohydrate in the meal is broken down into glucose (a sugar used as energy by your cells). The glucose enters your blood. Your pancreas senses the rising glucose and releases insulin. Insulin allows the glucose to enter your liver, muscle, and fat cells. Once your blood glucose starts to come back down, insulin levels come back down too. This cycle happens throughout the day. You eat a meal, glucose goes up, insulin goes up, glucose goes down, and insulin goes down. Insulin levels are typically lowest in the early morning since it's usually been at least 8 hours after your last meal.

It is the latter effect by which insulin has gotten its bad reputation. Because carbohydrate stimulates your body to release insulin, it has caused some people to argue that a diet high in carbohydrate will cause you to gain fat. Their reasoning, in a nutshell, goes like this:

However, this logic is based on many myths. Let's look at many of the myths surrounding insulin.

MYTH:A High Carbohydrate Diet Leads to Chronically High Insulin Levels

FACT:Insulin Is Only Elevated During the Time After a Meal In Healthy Individuals

One misconception regarding a high carbohydrate intake is that it will lead to chronically high insulin levels, meaning you will gain fat because lipogenesis will constantly exceed lipolysis (remember that fat gain can only occur if the rate of lipogenesis exceeds the rate of lipolysis). However, in healthy people, insulin only goes up in response to meals. This means that lipogenesis will only exceed lipolysis during the hours after a meal (known as the postprandial period). During times when you are fasting (such as extended times between meals, or when you are asleep), lipolysis will exceed lipogenesis (meaning you are burning fat). Over a 24-hour period, it will all balance out (assuming your are not consuming more calories than you are expending), meaning you do not gain weight. Here's a graph showing how this works:

After meals, fat is deposited with the help of insulin. However, between meals and during sleep, fat is lost. Fat balance will be zero over a 24-hour period if energy intake matches energy expenditure.

This is just a rough chart that I made, but the green area represents the lipogenesis occuring in response to a meal. The blue area represents lipolysis occuring in response to fasting between meals and during sleep. Over a 24-hour period, these will be balanced assuming you are not consuming more calories than you expend. This is true even if carbohydrate intake is high. In fact, there are populations that consume high carbohydrate diets and do not have high obesity rates, such as the traditional diet of the Okinawans. Also, if energy intake is lower than energy expenditure, a high carbohydrate diet will result in weight loss just as any other diet.

MYTH: Carbohydrate Drives Insulin, Which Drives Fat Storage

FACT: Your Body Can Synthesize and Store Fat Even When Insulin Is Low

One of the biggest misconceptions regarding insulin is that it's needed for fat storage. It isn't. Your body has ways to store and retain fat even when insulin is low. For example, there is an enzyme in your fat cells called hormone-sensitive lipase (HSL). HSL helps break down fat. Insulin suppresses the activity of HSL, and thus suppresses the breakdown of fat. This has caused people to point fingers at carbohydrate for causing fat gain.

However, fat will also suppress HSL even when insulin levels are low. This means you will be unable to lose fat even when carbohydrate intake is low, if you are overeating on calories. If you ate no carbohydrate but 5,000 calories of fat, you would still be unable to lose fat even though insulin would not be elevated. This would be because the high fat intake would suppress HSL. This also means that, if you're on a low carbohydrate diet, you still need to eat less calories than you expend to lose weight.

Now, some people might say, "Just try and consume 5000 calories of olive oil and see how far you get." Well, 5000 calories of olive oil isn't very palatable so of course I won't get very far. I wouldn't get very far consuming 5,000 calories of pure table sugar either.

This is probably the biggest misconception that is out there. Carbohydrates get a bad rap because of their effect on insulin, but protein stimulates insulin secretion as well. In fact, it can be just as potent of a stimulus for insulin as carbohydrate. One recent study compared the effects of two different meals on insulin. One meal contained 21 grams of protein and 125 grams of carbohydrate. The other meal contained 75 grams of protein and 75 grams of carbohydrate. Both meals contained 675 calories. Here is a chart of the insulin response:

Comparison of insulin response between low protein, high carb meal and high protein, low carb meal

You can see that, despite the fact that the blood sugar response was much higher in the meal with more carbohydrate, the insulin response wasn't higher. In fact, the insulin response was somewhat higher after the high protein meal, although this wasn't statistically significant.

Some people might argue that the "low-carb" condition wasn't really low carb because it had 75 grams of carbohydrate. But that's not the point. The point is that the high-carb condition had nearly TWICE as much carbohydrate, along with a HIGHER glucose response, yet insulin secretion was slightly LOWER. The protein was just as powerful at stimulating insulin as the carbohydrate.

I can also hear arguments coming like, "Yeah, but the insulin response is longer and more drawn out with protein." That wasn't true in this study either.

Insulin response to high protein and high carb meals

You can see in the chart that there was a trend for insulin to peak faster with the high protein condition, with a mean response of 45 uU/mL at 20 minutes after the meal, versus around 30 uU/mL in the high carb condition.

This tendency for a higher insulin response was associated with a tendency towards more appetite suppression. The subjects had a tendency towards less hunger and more fullness after the high protein meal:

Comparison of low protein, high carb and high protein, low carb meals and their effects on hunger and fullness

Here's the results of another study that compared the effects of 4 different types of protein on the insulin response to a meal. This study was interesting because they made milkshakes out of the different proteins (tuna shakes???? YUCK!!!!! Of course some people may remember the tuna shake recipes from the misc.fitness.weights days). The shakes contained only 11 grams of carbohydrate, and 51 grams of protein. Here's the insulin response to the different shakes:

Insulin Response to 4 Different Proteins

You can see that all of these proteins produced an insulin response, despite the fact that the carbohydrate in the shake was low. There was also different insulin responses between the proteins, with whey producing the highest insulin response.

Now, some might argue that the response is due to gluconeogenesis (a process by which your liver converts protein to glucose). The thought is that the protein will be converted to glucose, which will then raise insulin levels. As I mentioned earlier, people will claim that this will result in a much slower, more drawn-out insulin response, since it takes time for your liver to turn protein into glucose. However, that's not the case, because the insulin response was rapid, peaking within 30 minutes and coming back down quickly at 60 minutes:

Insulin response to different types of protein

This rapid insulin response was not due to changes in blood glucose. In fact, whey protein, which caused the greatest insulin response, caused a drop in blood glucose:

Glucose response to different types of protein

The insulin response was associated with appetite suppression. In fact, the whey protein, which had the highest insulin response, caused the greatest suppression of appetite. Here's a chart showing the calorie intake of the subjects when they ate lunch 4 hours after drinking the shake:

Calorie intake at a lunch consumed 4 hours after consuming various protein

The subjects ate nearly 150 calories less at lunch when they had whey protein, which also caused the greatest insulin response. In fact, there was an extremely strong inverse correlation between insulin and food intake (a correlation of -0.93).

Here's data from another study that looked at the insulin response to a meal that contained 485 calories, 102 grams of protein, 18 grams of carbohydrate, and almost no fat:

Insulin response to a high protein, low carb meal in lean and obese people

You can see that the insulin response was exaggerated in the obese subjects, probably due to insulin resistance. Here's a chart of the blood glucose response. You can see there was no relationship between the glucose response and insulin, which was similar to the study discussed earlier.

Blood glucose response in response to a high protein, low carb meal in lean and obese

The fact is that protein is a potent stimulator of insulin secretion, and this insulin secretion is not related to changes in blood sugar or gluconeogenesis from the protein. In fact, one study found beef to stimulate just as much insulin secretion as brown rice. The blood sugar response of 38 different foods could only explain 23% of the variability in insulin secretion in this study. Thus, there's a lot more that's behind insulin secretion than just carbohydrate.

Some might say, "Well, sure, protein causes insulin secretion, but this won't suppress fat-burning because it also causes glucagon secretion, which counteracts insulin's effects." I mentioned earlier how insulin will suppress lipolysis. Well, some people think that glucagon increases lipolysis to cancel this out.

It should be remembered why glucagon is released in response to protein in the first place. Since protein stimulates insulin secretion, it would cause a rapid drop in blood glucose if no carbohydrate is consumed with the protein. Glucagon prevents this rapid drop in blood sugar by stimulating the liver to produce glucose.

Insulin: Not Such a Villain After All

The fact is that insulin is not this terrible, fat-producing hormone that must be kept as low as possible. It is an important hormone for appetite and blood sugar regulation. In fact, if you truly wanted to keep insulin as low as possible, then you wouldn't eat a high protein diet...you would eat a low protein, low carbohydrate, high fat diet. However, I don't see anybody recommending that.

I'm sure some are having some cognitive dissonance reading this article right now. I know because I experienced the same disbelief years ago when I first discovered this paper and how protein caused large insulin responses. At the time, I had the same belief that others have...that insulin had to be kept under control and as low as possible, and that spikes in insulin were a bad thing. I had difficulty reconciling that study and my beliefs regarding insulin. However, as time went on, and as I read more research, I learned that my beliefs regarding insulin were simply wrong.

Now, you may be wondering why refined carbohydrates can be a problem. Many people think it's due to the rapid spikes in insulin. However, it's obviously not the insulin, because protein can cause rapid spikes in insulin as well. One problem with refined carbohydrate is a problem of energy density. With refined carbohydrate, it is easier to pack a lot of calories into a small package. Not only that, but foods with high energy density are often not as satiating as foods with low energy density. In fact, when it comes to high-carbohydrate foods, energy density is a strong predictor of a food's ability to create satiety (i.e., low-energy density foods create more satiety). There are other issues with refined carbohydrate as well that are beyond the scope of this article.

The bottom line is that insulin doesn't deserve the bad reputation it's been given. It's one of the main reasons why protein helps reduce hunger. You will get insulin spikes even on a low-carb, high-protein diet. Rather than worrying about insulin, you should worry about whatever diet works the best for you in regards to satiety and sustainability. As mentioned in a previous article, individual responses to particular diets are highly variable and what works for one person will not necessarily work for another. I will be writing a post in the future on the need for individualized approaches to nutrition.

I am following a “primal” way of eating which is high fat (55), regular protein (30), low carb (15). Of course these are just approximate numbers and I think that stressing about percentages is not healthy. Low carb is easily achieved, not because I’m carbophobic, but because I took off processed foods and grains (again if I want some bread some day, no stress), which I think are not optimal for reasons other than insulin. You’re then left with fruits and veggies, from which it is difficult to get more than about 15% carbs.

I cant wait for your article about how different diets apply for different people. I’m reading Lyle McDonald’s articles about the same issue in the meanwhile.

You state this
“The fact is that insulin is not this terrible, fat-producing hormone that must be kept as low as possible. It is an important hormone for appetite and blood sugar regulation. In fact, if you truly wanted to keep insulin as low as possible, then you wouldn’t eat a high protein diet…you would eat a low protein, low carbohydrate, high fat diet. However, I don’t see anybody recommending that.”
I ask Why NOT?
No-one has shown that a low carb /high fat diet is harmful. In fact it was shown as long ago as 1926, by Stefansson, to be a safe way of eating. Carbs have NEVER been shown to be necessary Some protein is essential for growth in children and repair in adults, but we don’t need much.

A bit of irony in there. Biggest insulin response was for whey and leucine. Guess what’s the mainstay of the first two weeks of the Eades misguided 6 Week Cure for the Middle Aged Middle diet? LOL Most of the folks who tried that diet lost most of their weight those first two weeks. Although they never gave a reason, the Eades were adamant about you getting in your shakes. Insulin was coarsing through my veins!

In fact, if you truly wanted to keep insulin as low as possible, then you wouldn’t eat a high protein diet…you would eat a low protein, low carbohydrate, high fat diet. However, I don’t see anybody recommending that.

Actually there is a growing cadre of folks advocating just that. It was the inspiration for Jimmy Moore’s eggfest that was more of a butter fest in the first weeks. Also the Silver Cloud diet of Atkins protege Salerno is essentially modeled on the Atkins “Fat Fast”. This diet is 80+% fat and and close to zero carb and 5-6 200 cal “meals”. Then there’s the Optimal Diet (Kwasniewsky) although it allows a few more carbs.

My personal opinion on these diets is that they will necessarily cause loss of LBM. I don’t see how they cannot. Rapid weight loss will be ensured by the rather severe calorie restriction (e.g. 1000-1200 cal for SC/Atkins FF), metabolic cost of gluconeogenesis and loss of endogenous protein. If one is eating essentially no carbohydrate, then the body has to generate roughly 130g per day from amino acid substrates. It can make some from the glycerol of fats, but it would also have to synthesize glycerol for re-esterification of all that dietary fat. Most of these diets are quite low protein. For example I think by OD guidelines I should be consuming 60g-75g protein that would allow for up to 50g carb meaning my body would have to manufacture 80g or so. Unless the glucose needs/usage of the body are being wildly overestimated (and I don’t think this is the case) such a diet would be protein deficient. On SC, protein intake would be like 40-50g (and Dr. Salerno treats patients on this diet for extended periods whereas Atkins suggested a week at most if memory serves) and ingesting trace carbs almost all of the glucose would have to come from protein.

I would add that near as I can tell, the Atkins Fat Fast was specifically designed to treat those with extreme insulin resistance to lower insulin levels. That is why the meager protein rations are split between 5-6 “meals”.

But it is telling that Atkins also severely limited calories. If fat calories had nothing to do with fat accumulation there would have been no need for this. I think Atkins knew just about anyone will lose weight eating like this and catabolizing some LBM in the process, but if left to their own devices to “eat when hungry, stop when full” of foods like cream cheese and mayo, absent protein’s satiating effect, Atkins needed to “mandate” severe caloric restriction rather than it occurring naturally.

“Arteriovenous NEFA concentration differences across the forearm did not change with either oral or intravenous lipid load. This suggests that there is no release into the circulation of LPL-derived fatty acids from skeletal muscle. This efficient entrapment of fatty acids in skeletal muscle occurred despite a high-fat load and lack of an insulin response. This is in contrast to what is seen in adipose tissue, where there is no significant trapping of fatty acids in the tissue with either oral or intravenous fat load.”

“With both oral and intravenous fat load, NEFA transcapillary flux across adipose tissue was strongly negative (outward flow) in the fasting state, becoming close to zero at 180- 240 min before becoming strongly negative again (Fig. 7A). After a mixed meal, NEFA transcapillary flux becomes positive after 60 min and stays strongly positive until at least 300 min (15). The different responses can be attributed partly to the lack of reesterification after fat loading and partly to the earlier return of HSL activity.”

“These results suggest that insulin is not essential for HSL suppression or LPL activation in the postprandial period but may be important in reesterification of NEFA in adipose tissue, thus affecting NEFA partitioning between adipose tissue and the circulation.(…) Insulin may therefore be necessary to give precise control to the pathway of net fat storage.”

Regarding protein as insulin stimulator, the studies you cite have virtually no fat in the test meals. Fat attenuates the insulin response. It seems that you are implying that higher protein meals (independent of the content of carbohydrate of fat) will produce higher postprandial insulin levels than high carbohydrate meals. If this was the case, you wouldnt see such differences between LF-HC diets and LCHF on insulin and glucose, both basal and post prandial.

On the other hand:

“MYTH: Insulin Makes You Hungry”

The correct answer isnt that insulin makes you hungry, insulin swings make you hungry.

“With both oral and intravenous fat load, NEFA transcapillary flux across adipose tissue was strongly negative (outward flow) in the fasting state, becoming close to zero at 180- 240 min before becoming strongly negative again (Fig. 7A). After a mixed meal, NEFA transcapillary flux becomes positive after 60 min and stays strongly positive until at least 300 min (15). The different responses can be attributed partly to the lack of reesterification after fat loading and partly to the earlier return of HSL activity.”

This mixed meal only contained 10 grams of carbohydrate. Remember that a low-carb diet is not carbohydrate-free. Thus, on a low-carb diet, NEFA re-esterification and fat deposition will still occur if intake exceeds expenditure.

You also didn’t mention this statement from the paper: “Intracellular lipolysis, as shown by the calculated rate of HSL action, was suppressed almost completely with both oral and intravenous fat load“. This was despite the fact there was no elevation of insulin.

Regarding protein as insulin stimulator, the studies you cite have virtually no fat in the test meals.

This is not true, as I had referenced the Holt paper which showed equal insulin responses when comparing beef (which contains fat) to brown rice. They also showed a large insulin response to cheese, which is very low in carbohydrate, yet high in fat and protein.

Fat attenuates the insulin response

Do you have evidence for this statement, beyond a slowing of gastric emptying? The Evans paper showed little change in plasma insulin in response to the intravenous fat load.

It seems that you are implying that higher protein meals (independent of the content of carbohydrate of fat) will produce higher postprandial insulin levels than high carbohydrate meals.

No, I never made such an implication. The point is that protein can be nearly just as potent of a stimulus for acute insulin secretion as carbohydrate.

If this was the case, you wouldnt see such differences between LF-HC diets and LCHF on insulin and glucose, both basal and post prandial

Basal insulin levels are not relevant to protein as an acute stimulator of insulin secretion. Regarding post-prandial levels, I’m talking about meals and not diets. A LCHF diet may reduce postprandial insulin responses over a period of weeks due to less insulin resistance, but LCHF meals will still cause significant increases in insulin if they are high in protein.

The correct answer isnt that insulin makes you hungry, insulin swings make you hungry.

This is often stated, but there is little evidence for this. If insulin swings were responsible for inducing hunger, then the study examples given should’ve caused more hunger with higher protein intakes (because they caused greater insulin swings), yet they showed less hunger. Interestingly, here’s another paper showing greater satiety with a high glycemic meal (which caused a greater insulin response) over 8 hours than a low glycemic meal.

Note that I’m not advocating a diet rich in high glycemic carbohydrate. I’m just pointing out that the concept of “insulin swings causing hunger” doesn’t hold up in scientific experiments.

Our point was that it’s not suprising that little reesterification was occurring because there’s not a lot of substrate available for glycerol phosphate synthesis when the diet contained only about 10 grams of carbohydrate and 3 grams of protein. This is not a typical low-carb meal (especially the protein content).

“It may also be that the mere lowering of serum insulin concentrations, as
is seen with LCDs, may lead to a reduction in appetite. In support
of this idea, several studies have found that insulin increases food
intake, that foods with high insulin responses are less satiating,
and that suppression of insulin with octreotide leads to weight
loss” – Westman et al. Low-carbohydrate nutrition and metabolism, Am J Clin Nutr 2007;86:276–84

The point is that protein can be nearly just as potent of a stimulus for acute insulin secretion as carbohydrate.

Basal insulin levels are not relevant to protein as an acute stimulator of insulin secretion. Regarding post-prandial levels, I’m talking about meals and not diets. A LCHF diet may reduce postprandial insulin responses over a period of weeks due to less insulin resistance, but LCHF meals will still cause significant increases in insulin if they are high in protein.

Yes, indeed protein can stimulate insulin depending on the source (being whey one of the most potent). But as I have said, fat and fiber can attenuate the insulin response to protein ingestion. What is relevant is the effect of the diet, not just a single meal. A LCHFD will result in more insulin reduction than a HCLF.

Basal insulin levels are not relevant to protein as an acute stimulator of insulin secretion.

There are studies where fat added to carbohydrate meals increase the insulin response, others show that fat reduces it. I have found one study where fat increased the insulin response to protein. (http://www.ajcn.org/cgi/content/abstract/37/6/941)

The problem interpreting these results is that the response is measured only for a couple of meals (no long term effect) and individual variation is important regarding insulin secretion. As I have said before, what is relevant is the effect that a diet has on postprandial and basal insulin levels, not a single meal. You can see that after a LCKD the postprandial insulin response is reduced (http://www.metabolismjournal.com/article/S0026-0495(01)56546-4/abstract). So if you test the same meal before and after the diet you get different insulin responses.

I recently stumbled on your site via Alan’s weblog. I had a very informative time reading your articles.

Little confused though by this sentence:
”Insulin doesn’t just regulate blood sugar. It has other effects as well. For example, it stimulates your muscles to build new protein (a process called protein synthesis)”

I was always under the impression insulin only has a permissive role in MPS. It does prevent MPB, but only with a marginal raise (15 mU/l Rennie et al. 2006). Supraphysiological do however stimulate MPS (1000 fold increase).
I haven’t read the fulltext of the study you referenced but the abstract reveales insulin was given by infusion. Where these levels supraphysiological? If so, this isn’t relevant for normal people. If not, how can you explain the discrepancy between this study and the other data?

Thanks for your comment. The confusion regarding insulin and protein synthesis comes from differences in study design. From the paper I referenced:

The notion that insulin stimulates skeletal muscle protein synthesis in adult humans has long been debated because some studies reported that insulin administration was unable to stimulate muscle protein synthesis while it decreased protein breakdown (8, 9, 21), whereas several others reported an increase in protein synthesis with no change in breakdown (6, 46–48).We have previously discussed this issue at length (10–12, 18), suggesting that differences in vasodilation and amino acid delivery might have explained these discrepancies. Studies reporting reduced proteolysis with no change in protein synthesis employed systemic insulin administration in the absence of exogenous amino acid administration, resulting in decreased amino acid concentration and delivery (9, 21, 49). Conversely, studies reporting increased protein synthesis prevented hypoaminoacidemia using local insulin administration (as in the present study) or systemic infusion with amino acid coinfusion (6, 46–48, 50). The present study provides the mechanistic proof that our original hypothesis is correct, showing not only that blockade of insulin induced vasodilation prevents the increase in protein synthesis but also that when this occurs in a subject with an otherwise intact insulin signaling apparatus, proteolysis decreases with a consequent protein-sparing effect.

I dug up the full-text of the first study and read Lucas’s reference but honestly most is way above my head. I have no background in physiology or exercise science whatsoever, just a genuine interest in the science behind bodybuilding.

But what does this mean for practical applications? Where the good old bro’s right and is ‘spiking up ur insulin’ a good thing afterall?

In terms of practical application, it doesn’t mean you purposely try to cause insulin spikes. It is more to dispel the notion that insulin spikes are inherently a bad thing. I will be a doing a follow-up post on this in the future, and discuss a drug that actually restores insulin spikes in type 2 diabetics and also causes weight loss.

The take home message is that insulin is released every time you eat. Insulin has a permissive role in MPS and MPB, as shown in the paper I linked. For switching the net protein balance after a workout you need aminoacids and insulin, period. Now the problem is you dont need that much insulin to get its maximal effects. The threshold seems to be around 30-60uU/mL. Consider that a whey protein shake (most widely used PWO) is very insulinogenic.

Once again, thank you for posting this article. I hope that some folks will have some enlightenment regards to insulin especially the people from low carb talibans. I will link this article to several sites.

So… we can store fat very easily even w/o the presence of insulin. But I’ve read that we can’t access those fat stores when insulin is high, and in healthy people, like you said, insulin and blood sugar go down after a meal (so they don’t stay high)- but what about in overweight/obese people? My impression from what I’ve read about nutrition is that the problem is insulin resistance. So what do you think causes/contributes to that aside from excess calories?

There are many causes to insulin resistance, including, but not limited to, sleep loss, stress, inactivity, certain medications, etc. Many of these things act synergistically to create a “perfect storm”, resulting in the high prevalence of insulin resistance and metabolic syndrome we have in our society.

Do we have any studies showing that we can induce insulin resistance by overfeeding protein? I’m not aware of any.

Presumably, insulin resistance could be induced by protein portions just as readily as with an equivalent portion/s of insulinogenic carbohydrate (i.e. by a portion of carb that provokes the same insulin response as the portion of protein)?

I’m wondering about this, and hypothesising that perhaps insulin resistance isn’t merely a response to hyperinsulinemia (brought about by excessive carbs or proteins), but is actually a response to hyperglycemia? This would explain why excessive protein doesn’t seem to induce insulin resistance in the way excessive carbs do, even though it elicits a similar insulin response (i.e. because it doesn’t provoke a corresponding rise in blood sugar).

I’m not aware of any studies specifically overfeeding on protein and looking at insulin resistance.

The whole concept of insulin resistance and hyperinsulinemia is a chicken/egg problem that scientists still haven’t quite solved. There is data indicating insulin resistance to come first, with hyperinsulinemia as a compensatory mechanism, but there’s also data indicating hyperinsulinemia to contribute to insulin resistance. It may very well be that it works both ways. I personally believe that, in most cases, it starts with insulin resistance leading to hyperinsulinemia. The scientific data definitely supports that there are many causes to insulin resistance.

Very good read indeed. And your FACTS counteracting the MYTHS are solid for as long it concerns healthy (exercising) people. To bad there are not many healthy people left. A lot already suffer from insulin resistance or are on their way. They are kept sugar addicted by the dietary guidelines dictated by the industry. Insulin resistance is, as you know, the precursor for the diseases of civilization. I made an easy to follow post/video on the subject http://bit.ly/d4oVSz. Solution? First cut the carbs then get healthy and bring (controlled quantities of) good carbs back into your diet. VBR Hans

The information in this article applies to insulin resistant people as well. For example, I cited one study on obese, insulin resistant people where a high protein meal caused a large insulin spike, larger than what was found in heatlhy, normal weight people. Yet we know that high protein diets can be beneficial for people who are insulin resistant.

The key for improving insulin resistance is not insulin control, per se. It is improving blood glucose control and insulin sensitivity. Cutting carbs can certainly help with that, but it’s not the only way.

Fantastic article. I’ve been looking for solid info on why high carbohydrate foods that briefly stimulate insulin are far less dangerous than having insulin levels chronically elevated. You really opened my eyes to some new ideas to add to my understanding of health.

I’m still not convinced that the “energy density” of refined carbs are much of an issue. The calorie density of fat is far greater than that of carbs, which is one of the reasons the “low fat” gang has been able to rule popular opinion for the past few decades. (And we all know how well that’s been working.) The issue of satiation and hormonal dischord (especially relating to leptin resistance and hyperinsulinemia) is still likely the crucial player.

Thanks for your comment. I also think there’s more to it than physiological factors. There are complex psychological factors that also play a role in human eating behavior. Many of these interact with the physiological factors to contribute to the obesity problem. I am looking to write a book on this in the future.

Do we? Has anybody really followed the low fat diet? Not to imply that I’m a low fat proponent, I’ve never tried it either! lol. But with the massive amounts of processed food, fast food, and restaurant food that Americans eat, I can’t imagine more than a very small percentage of Americans have actually followed a low fat diet for a significant period of time. Unless you meant that the low fat gang’s advocacy for a low fat diet, their ability to persuade or influence people to implement the diet, has been a total failure. In that case, I would wholeheartedly agree! 🙂

We as a nation have been on a low-fat diet since 1977’s “Dietary Goals for the United States” started demonizing fat based on half-baked evidence. While it is true that total average caloric intake has risen in this time, total calories from fat has fallen. I’ve known so many people who have been on low fat diets (including myself) that I have lost count.

The issue comes when you start demonizing foods that have successfully sustained human populations for generations, if not millions of years. Half the time I can’t find full-fat yogurt at the grocery store but have my choice of dozens (if not hundreds) of low-fat or non-fat alternatives. A walk down every aisle will show you product upon product proudly proclaiming its lack of fat.

When you take Real Food and remove the fat, you are left with a product that tastes like cardboard. So food companies add all sorts of extra junk (specifically sugar or HFCS) so they can sell the stuff.

Even if you made no conscious decision to follow it, it is difficult to NOT follow a low fat diet today. (I can’t tell you how many households I’ve gone to that STILL use margarine.)

My point is this: the majority of Americans ARE on a low-fat diet. Especially compared to how we ate in the past and most especially when you consider the diet we most likely evolved on: lots of fatty, vitamin-rich organs and bone marrow, which few people consume today.

But the rise in obesity and mortality rates due to diet-related diseases are all the testament needed to see that what we are doing isn’t working.

While it is true that total average caloric intake has risen in this time, total calories from fat has fallen.

Percentage of calories from fat has fallen, but total absolute fat intake has actually increased. The bottom line is that Americans are eating more of everything….carbs AND fat, although the absolute carbohydrate intake increased to a greater degree.

One other thing of note. I would agree with you that fat has been unfairly demonized. However, it is this demonization that will also lead to an underreporting of fat intake among the populace. Data on macronutrient intake of the U.S. population is based off of self-report and survey data. It is well known that people underreport their food intake. It is also known that people will selectively underreport foods that are considered “bad”, which would include fat. So the fat intake of the U.S. population is likely underreported.

I would also agree that what we’re doing isn’t working. But this brings up an important point…is there anything that can be done from a public policy perspective? Maybe not. The problem is that obesity is a multifactorial problem, with numerous variables all interacting with each other to cause the problem. This means that any univariate solution (like lowering fat intake) is doomed to fail in the long run. Getting people to change their lifestyle is extremely difficult. We know it is difficult on an individual basis, which means it would be even more difficult on a population-wide basis.

Good point that people are likely underreporting how much fat they are consuming. Wouldn’t surprise me one bit.

But my biggest beef with the “low-fatting” of the world is the garbage they put in food to take the place of the fat. Sugar, HFCS, artificial flavors all are called in to stand in for flavor.

Another big problem is the rapid adoption of “factory fats” primarily composed of unsaturated fats to appease the anti-sat fat crowd. We have, for the most part, come to our senses about the dangers of trans fats, but have still called on corn oil, soybean oil, and others to take care of a large part of our fat needs. These highly-processed oils haven’t been in our diets long enough to give us an idea of their impact, but the resulting massive rise in inflammation-causing linoleic acid causes me a bit of concern.

In the end, I agree with you that this is a complex problem with no easy answers. Although it is not THE answer, I have found that the “highest leverage” solution is to focus on eating Real Food rather than Food Products. Stop deconstructing food into macro- and micro-nutrients and start focusing on the quality and provenance of the food, along with its track record of successfully sustaining human populations. Most problems will take care of themselves with just this guideline.

I definitely agree with you on the “low-fatting”. People see “low-fat” on the label and think they can consume as much as they want. And you are correct that many low-fat foods also are highly processed and high in refined carbohydrate.

I also agree with you regarding real food. When we look at many healthy populations, we see a wide range of macronutrient intakes, such as high carb in Okinawans or moderate carb in the Mediterranean diet. But the common theme is a reliance on predominantly whole, unprocessed foods.

While eating out is certainly not conducive to any type of diet, I’m more concerned with the type of fat you find in restaurants (highly processed) than the amount. And it seems like every restaurant I go to advertises one or several “healthy dishes” based on their low fat content.

Nope. You challenged my belief that The Low Fat Diet Fad has been an utter failure, remember? My issue is not with the specific ratio of macronutrients than with the stuff they put in the food to take the place of the fat. Implied within the low fat scare is the even bigger fear of saturated fat, which has led to people relying more on processed vegetable oils (higher in unsat fat) over the more traditional animal fats (higher in sat fat).

I live in the middle of San Diego and haven’t yet found full fat yogurt in my enormous Ralph’s. Consider yourself lucky!

Yes. It is more difficult to eat high-fat than low-fat these days. As you might have guessed, I’m not big on the processed foods, but let’s look at the foods you listed from what I remember seeing at the grocery store:

Burgers: I have to bend over backwards to get some good fatty burgers. (aka the only kind anyone ate up until the low fat fad started.) But I can find a mountain of 90% lean at the store. Yech!

Ice cream: Same problem I see with all dairy. “Low fat” or “nonfat” is the norm now.

Pizza, cookies, fries, donuts: Can’t say I’ve eaten any of these in a while, but I wouldn’t be surprised if the lowfat and nonfat varieties have taken over the supermarkets. I remember as a kid eating SnackWells cookies because that’s all my mom had. Again, yuck.

Ultimately, whether we are eating less fat or not us irrelevant. What IS relevant is the onslaught of garbage that has entered our diets as food companies have sought to meet the consumer demand for low fat products while still retaining palatability.

Dude, seriously, if you can’t find foods high in fat in grocery stores, you must be wearing a blindfold! The checkout lane, the bakery, the ice cream section, anywhere! Couldn’t be easier. If you don’t see them, you must be doing it on purpose to force reality to conform to your ideology.

First off, you’re damn right I force reality to conform to my ideology! EVERYONE does it! (Hint: that means you, too.) For me to deny that would be outright dishonest.

But perhaps I was unclear when I said that it is more difficult to eat high-fat than low-fat these days. I mean that compared to any time in the past, a person on autopilot set free in a grocery store will wind up at the checkout with more items artificially reduced in fat than ever before.

Okay, but what about the “new foods” that you listed? Yes, those Little Debbies, Oreos, funnel cakes, Easy Cheeses, Zagnuts, blah blah blah are all high in fat. But what are you forgetting? They are jacked up with sugar as well!

You and I obviously aren’t talking about the same thing when it comes to the definition of a low fat diet. I’m talking about the U.S. Government–sanctioned definition of a “healthy diet”: no more than 20-35% calories from fat, with no more than 10% of that from saturated fat. You seem to be talking about total fat, which of course has gone up as caloric intake has skyrocketed. Or maybe you’re talking about an uber-low-fat, a la Dean Ornish, I’m just not sure.

But I am sure that you are just as set in your idealogy as I am in mine.

“First off, you’re damn right I force reality to conform to my ideology!”

Then this debate is pointless. It’ll just go on and on and lead nowhere. You’ll never see the obvious reality staring you in the face because you’re so blinded by your ideology- or rather, your dogma.

High fat is high fat, regardless of the sugar content. Butter, vegetable oils, and nut butters are high in fat, too. They’re also extremely energy dense, and can easily add several
hundred calories to one’s diet if one isn’t careful.

Nobody pays attention to government recommendations. (Calorie counts in restaurants don’t seem to make much of a difference, either.) They eat what they want, when they want, however much they want. And much of what they want is high in fat.

The only “ideology” I have regarding weight loss is that it is necessary to create and adhere to a calorie deficit. That’s based on reality. It’s not dogma.

Hey, I’m just busting your balls with the Beavis comment. With the pushback you’ve been giving, you didn’t expect me to be to give you THAT much leniency, did you? Plus, things are just getting WAY too serious around here!

The longer this goes on, the more it focuses on completely irrelevant things (the impact of dietary fat upon the incidence of overweight and obesity) vs. my original point (the low-fatting of our society has caused more damage to our health than almost any other factor due to the rapid adoption of food products in place of real food). But hey, you gotta have some kind of charisma for me to keep going this long on such an asinine subject, right?

I get the impression that you aren’t understanding me, so I will reiterate my previous points and further connect the dots to ensure that I am crystal clear about my original claim.

Since 1977, our country has been on a low fat diet. This was spurred on, in large part, by a governmental push with the publication of “Dietary Guidelines for Americans.” A healthy diet, according to the government, contains 20 – 35% calories from fat, no more than 10% of that saturated. It is this definition I will use when I refer to “a low fat diet.”

Now, I do not mean that in 1977 that the majority of Americans started following the government’s recommendations to a T and have persisted ever since. What I mean is that we have been making a concerted effort to follow these recommendations. And slowly but surely, we have arrived there.

As a result, most of the meat and dairy we eat has become leaner over the past three decades, and we have swapped out SFA-heavy animal fats such as butter and lard for more MUFA- and PUFA-heavy vegetable oils such as corn oil and soybean oil. Not only this, but many of the food products have come out with low fat alternatives.

So perhaps it would be more accurate for me to say that since 1977, Americans on average have slowly altered their diets in an effort to conform with the government’s recommendations of 20-35% of calories from fat, no more than 10% of which from SFA.

Now to your comments.
You seem to want to write me off because:
1. I disagree with conventional wisdom.
2. I disagree with you.
3. I am assertive about my beliefs.
This is nothing but a lazy cop-out on your part.

First off, you accused me of being “totally consumed and absorbed by (my) ideology.” I owned up to being susceptible to my beliefs affecting my perception, which you took as evidence that “(I’ll) never see the obvious reality staring (me) in the face because (I’m) so blinded by (my) ideology- or rather, (my) dogma.”

You deceive yourself all the time, Jordan. We all do… I cannot stress this enough. Do not get up in your high tower and declare your complete objectivity like this. It’s completely ridiculous. One of the most insidious characteristics of self-deception is that it covers its own tracks. Therefore, we convince ourselves all the time that we are right just because the beliefs we have are OUR beliefs, and if anyone else disagrees with us, they are flat wrong. No questions asked.

Read Daniel Goleman’s fantastic book “Vital Lies, Simple Truths.” It is all about this cognitive bias and will help you understand how much of an impact it has on human cognition.

Confession time. Half of what I know is wrong, but I don’t know which half that is. (Hardly the words of an ideologue, wouldn’t you say?) Your disagreement with my assertion that our country has been on a low fat diet since 1977 caused some cognitive dissonance within me, and I was eager to hear your reasoning. But you gave me nothing to go on other than your conviction that you must be right because it is your belief.

Your claim that “this debate is pointless. It’ll just go on and on and lead nowhere” because I freely admitted that I am susceptible to bias is total B.S. A bigger threat to this discussion going nowhere is not my belief in personal fallibility, but your belief in knowledge of absolute truth. I am fully open to your case, but you have given me nothing – NOTHING – of any substance.

For laughs, I am going to challenge your claim to Knowledge of Absolute Truth and Objectivity:

“The only ‘ideology’ I have regarding weight loss is that it is necessary to create and adhere to a calorie deficit. That’s based on reality. It’s not dogma.”

Well, it’s based on the first law of thermodynamics, which is about as close to absolute truth as we’re ever going to see. But you have made the same two baseless assumptions that most people have done.

Namely, that “calories in and calories out” are the cause (there is no such arrow of causality in the first law) and that these are both independent variables (in bomb calorimeters, yes. In animals with elaborate homeostatic systems as the result of eons of evolution, not so much.)

“I challenged your belief that most Americans have been on a low fat diet since 1977.”

Well, my exact words were “we as a nation have been on a low fat diet since 1977.” I attempted to further clarify this claim when I said “compared to any time in the past, a person on autopilot set free in a grocery store will wind up at the checkout with more items artificially reduced in fat than ever before.”

NHANES II, conducted between 1976 and 1980, found that, on average, men consumed 36.8% of their calories as fat, 13.2% of which was saturated. Women consumed 36.0% of their calories as fat, 12.5% of which was saturated.

NHANES 1999-2000 found men consumed 32.8% of their calories as fat, 10.9% of that saturated, while women consumed 32.8% of their calories as fat, of which 11.0% was saturated. Both men and women conformed to the total fat requirement of a low fat diet, while they were just outside the SFA requirement. And both cut both total fat and SFA as % of total calories during this time.

The 2000 census found the U.S. population to be 281,421,906. This, coupled with the NHANES data, leads me to believe it is not entirely unreasonable to deduce that at least 100 million Americans were on a low fat diet (as I and the government define it) in 2000.

This doesn’t do much for your claim that you “can’t imagine more than a very small percentage of Americans have actually followed a low fat diet for a significant period of time.”

“Anybody can see that most Americans eat an enormous amount of fatty foods.”

More vague generalities and subjectivity masquerading as objectivity.

Anybody could see that the sun, planets, and stars all orbited a stationary earth before Copernicus came along. You’re not going to convince me with that kind of logic, buddy.

And enormous compared to what? Certainly not compared to % calories from fat in 1977 (as was my original claim that you challenged). Again, you have refused to define “low fat diet” as clearly as I have and therefore can make claims like this without having to justify them.

Once again, I believe that “low fat diet” to you means either low in absolute fat (although you haven’t given the threshold of what is low and what is high) or you think it is a very low fat diet by % calories (10%? I don’t know. Help me out here!)

Again, I think we have different definitions and therefore this entire discussion is becoming a complete waste for both of us.

“High fat is high fat, regardless of the sugar content.”

There are two ways to reduce the fat content of a food (as I have defined it). First, you can reduce the concentration of fats within the food (which is intuitive). Second, you can INCREASE the concentration of protein and / or carbohydrate. Adding more sugar to a food means adding more carbohydrate, which means a lowering of the % calories from fat.

So yes, those Little Debbies may be high in absolute fat, but they are also high in absolute sugar, which allows food companies to sell junk like this as “low fat”. And if you truly think that the issue with Twinkies is that they have too much fat then I have a bridge made of fat free cookies to sell you.

“Nobody pays attention to government recommendations.”

Well, SOMEBODY must be paying attention for all the low fat garbage to take over my grocery store. Either consumers are demanding more low-fat products (d’oh!) or the food companies have been intimidated into flooding the market with fat-free food products, making it more difficult for me to get my fat on – my original gripe (double d’oh!).

So I still believe that our country has been on a low fat diet since 1977. During this time, we have been moving closer and closer towards the government’s definition of a healthy diet: 20 – 35% of calories from fat, with no more than 10% of that from saturated fat. According to NHANES 1999-2000, we have met the goal for total fat and fell just short of the goal for SFA.

During this same time, obesity has skyrocketed. Not only have we as a nation grown fatter and fatter, but the incidence of such “diseases of civilization” such as coronary heart disease, diabetes, and cancer have risen as well. The Low Fat Fad has been an abject failure.

Your challenge to this assertion seems to rest on the following factors:
1. Everyone knows we eat too much fat.
2. I am an ideologue.

Weak. Give me specifics. Quantify your reasoning and stop giving ad hominem arguments to back your theory. Because right now you just sound like another guy who unquestioningly accepts the status quo. And as far as I’m concerned, this debate is over until you can give me a more objective and thoughtful rebuttal.

Sorry, I don’t have time for another long, drawn out debate. I have to run to the store to buy some Oreo’s! And maybe some peanut butter cup ice cream! Oh, and maybe some chocolate covered pretzels, too! lol. I agree, things are getting too serious around here. 🙂

I’ve lost 62 pounds while still eating my fair share of high fat *and* high sugar treats, so this debate is totally meaningless for me, on a personal level. I eat what I like, just less of it. Mostly “healthy,” but not all healthy! I haven’t had to go low carb or Paleo, which makes me feel very, very grateful. God, either of those diets would be so miserable. Low carb would mean no ice cream, no chocolate, no cheesecakes, no cream pies, no pizza! Paleo would mean no baked potatoes, no popcorn, no homemade-style bread, no oatmeal, no beans and rice, no burgers with the bun! No, thanks! Count me out.

So anyway, I’ll resist doing a time-consuming point-by-point and write just two specific responses. You can have the last word if you want.

“During this same time, obesity has skyrocketed.”

Obesity has skyrocketed because too many of us have created and maintained calorie surpluses. Regardless of whether a food is *marketed* as low fat, low calorie, or low carb, if we create a calorie surplus, we gain weight. Regardless of whether we eat processed or unprocessed foods, if we create a surplus, we gain weight.

The “Insulin causes obesity” myth is probably one of the most popular myths disseminated by the fitness industry. This is a common example of a limited understanding of insulin’s influence on a mutltitude of bodily functions. It also demonstrates the tendency for people to base beliefs on authority and lack of crticial thinking ability, rather than science. Why do so many people belief this unfounded claim? Because their friend read it and told them so , or “they say”, or maybe their favorite fitness author said so.

When comparing diets- with equal calories- that result in hyperinsulinemia versus low-normal insulinemia fat loss is the same

I just finished reading your book for a second time; good stuff my friend!

Honestly, and speaking from the perspective of a “reformed fat bastard”, fat folks need a boogey-man to blame for their gluttony (which is an eating disorder no one wants to talk about …) and many are blissfully ignorant of the basics of fat loss.

Even in this day of easily accessible information, I find many people still don’t really think that calories are that important. And, I’m not talking about LC fanaticos either. I believe that so much marketing has caused the “basics” to be viewed as an option rather than the rule. This is why you see people asking “So, is it the carbs OR the calories?” as if they’re equal …

I wanted to ask you and James how much research is being spent on the psychological barriers that the obese face? I’m asking because I think that this is where the majority of research needs to be directed.

Hopefully Jamie will respond as well, but there is a lot of research that has looked at the various psychological, social, and cultural barriers that obese people face, which is why keeping weight off for the long term is so challenging no matter what type of diet someone uses. PubMed searches can help turn up a lot of information on this.

I would agree that the majority of future research should be geared towards behavioarl aspects of nutrition. Brian Wansink (book- Mindless Eating) does a good job addressing environmental factors and their affect on food intake

Good research, James. But I think that two of your conclusions are unwarranted, because they go beyond what your data shows. First, you have not proven that insulin suppresses hunger. You have only shown that foods which cause insulin to rise (protein and carbohydrate) also suppress hunger. Association does not imply causality. In fact, there are experiments reported by Taubes showing that injecting insulin without simultaneously supplying calories does cause a sudden increase in hunger. So a more plausible interpretation of the data you present here is that the foods (whey, tuna, etc.) are supplying hunger-suppressing peptides and sugars to the bloodstream, which simultaneously causes an insulin spike to begin removing the excess peptides and sugars into storage. The insulin could still be blunting the net appetite suppressing effect of this surge of nutrients. So your conclusion is unproven, and may actually be false.

Second, you have not proven that elevated insulin is harmless. Occasional intermittent insulin spikes are fine, so long as there are also long stretches of many hours where insulin levels are low. Your graph shows this nicely…why not increase the length of the intermittent fasting intervals even more? I have practiced intermittent fasting for a year, eating only one or two meals per day, and totally cutting out snacks. Combined with high intensity exercise, this allowed me to lose 30 pounds rather easily, including virtually all of my intra-abdominal fat. And my measured basal insulin levels dropped from 18 to 4 units. I’m sure there is a connection between the lower insulin and the weight loss. So while I agree with you that a few daily insulin spikes are fine, and perhaps even good, I’m not sure that it is a good idea to go too far in the direction of “insulin is harmless”.

In fact, there are experiments reported by Taubes showing that injecting insulin without simultaneously supplying calories does cause a sudden increase in hunger.

This is because insulin administration, in the absence of calories, causes hypoglycemia, which then induces hunger. So it is the hypoglycemia that causes the hunger, not the insulin. This is not the same situation as insulin secretion in a fed state and thus the two cannot be compared.

Second, you have not proven that elevated insulin is harmless.

This is a strawman in that I never claimed that elevated insulin is harmless. For example, chronic hyperinsulinemia secondary to insulin resistance certainly is a problem. But chronic hyperinsulinemia due to insulin resistance is a completely different issue compared to insulin elevation due to carbohydrate intake. My entire point is that the two should not be confused, and unfortunately many people do confuse the two.

I’m sure there is a connection between the lower insulin and the weight loss.

This is because weight loss increases insulin sensitivity, which then lowers fasting insulin levels. But the lower fasting insulin is not causing the weight loss…it is a result of the weight loss.

James, I’m still not convinced that insulin is not a primary driver of hunger. The brain infusion experiment you cited by Air et al injected very low doses of insulin directly into a brain ventricle “in doses that do not affect blood glucose”. First, this does not tell us what affect insulin would have if administered at the the higher levels typical of postprandial or even preprandial secretion. Perhaps insulin inhibits appetite at very low levels, in certain brain locations, but stimulates appetite at normal , higher levels. Biochemical regulation often exhibits such dose or location dependence, producing homeostatic feedback effeccts.

But more importantly, the direct infusion of insulin into the brain is not a physiologically realistic model of the way that insulin acts in the body simultaneously on multiple organs and tissues, removing glucose from the bloodstream, inhibiting the release of fatty acids from adipose tissue, and shifting liver metabolism. Such “isolation” techniques such as the study by Air et al can be hard to interpret. What may be the case is that insulin drives hunger initially, but by the time it reaches certain brain centers, it then has a compensatory inhibitor feedback effect. Without further evidence, I would suggest the hunger driving effect is the more dominant one.

A telling point point is that most people, conditioned to eat breakfast every morning, experience a surge of insulin upon waking. (Diabetics know this as the “dawn phenomenon”, and they typically “cover” it with a dose of injected insulin). During sleep, with insulin low, fatty acids have been mobilized all night, maintaining satiety. It is the insulin surge upon waking that suppresses fatty acid release, and may also cause blood sugar release, driving hunger and causing us to eat. A similar thing happens when we smell appetizing foods, or the dinner hour approaches, and pre-prandial insulin is secreted in response to olfactory or psychological cues, as Karen Teff and others have shown. Are you proposing that these changes in fatty acid and glucose availability happen spontaneously or without the agency of insulin? And that insulin is only secreted in response to meals, never in advance of eating behavior? If insulin is not the proximate agent here, what is?

Jacques Le Magnen’s experiments in the 1950s elegantly showed how levels of fatty acids, glucose and peptides in the blood are homeostatically controlled by storage hormones line insulin and mobilizing hormones like glucagon and adrenaline. Certainly, there is newer research which adds other hormones like HSL and leptin to the system, but the homeostatic principle is still valid.

I have been able to greatly decrease the amount of food I eat daily by intermittent fasting. I now rarely eat breakfast and only eat lunch on some days. Mainly I eat dinner, and I vary the time at which I eat it. I have essentially deconditioned my previous “schedule” of eating. My blood glucose measures very steady all day except right at meals. So clearly, appetite can be conditioned. The best explanation for the onset of hunger must be the agency of hormones such as insulin and leptin, under the control of brain centers which respond to physiological and psychological signals, and in turn which are able to regulate fatty acids and glucose that trigger hunger.

To say that hunger is primarily a response to low blood glucose leaves open the question of what causes blood glucose to drop. What is your answer to that, if it is not insulin? And how is it that body is able to integrate the balance of multiple fuels – glucose, fatty acids, ketones and peptides — unless driven by hormonal responses to environmental supply and demand?

>>> Seems a better candidate to produce hunger at regular feed times than insulin

would be better said:
is a good candidate for being part of the chain (IMHO maybe an earlier part of the chain) that controls hunger, along with leptin & low blood glucose & insulin & brain reward mechanisms

>> direct infusion of insulin into the brain is not a physiologically realistic model

But injecting fasted patients with insulin is, according to you and Gary Taubes

>>> The best explanation for the onset of hunger must be the agency of hormones such as insulin and leptin,

So who are you arguing with here? That’s been James’ point the entire time – many factors are involved. You somehow managed to write this sentence, and then just below mis-represent all of James’ preceding discussion into the simplistic

>> To say that hunger is primarily a response to low blood glucose

nobody claimed this as the general universal case, least of all James. The specific case that was being discussed was about insulin injection in fasted patients. James has gone out of his way to repeatedly state that hunger control is very complex

re-reading the entire post, I really don’t know what you’re arguing. The whole point of this series of articles is that Insulin is not the sole, univariate determinant of obesity, yet your post repeatedly supports this position, while somehow managing to argue with James.

Sorry to hear you thought my post was confusing. You may be right that I could have been clearer. Let me try again.

James states:

“MYTH: Insulin Makes You Hungry. FACT: Insulin Suppresses Appetite. It is a well known fact that insulin acutely suppresses appetite. This has been demonstrated in dozens and dozens of experiments.”

I will acknowledge that cause-and-effect relationships can be complex. Some causal trains can even be circular or cyclic: For example, obesity causes insulin resistance, which typically leads to further weight gain. But even in complex systems, one can often single out a significant or driving cause. In his above statement, James is the one taking a rather black-and-white position here. He flat out denies that insulin can make you hungry, calling it a “myth”. According to the statement above, insulin can ONLY suppress appetite.

Now I am not denying that insulin might be able to have an inhibitory or suppressive effect on appetite. Based upon the experiments James cites, it appears that insulin can in fact suppress appetite when administered directly to certain regions of the brain, at certain doses, in certain situatioins. And in normal physiology, I acknowledge that this might be plausible and useful as a self-limiting way of putting the brakes on appetite after a big meal.

But I believe there is evidence that insulin can ALSO increase appetite. I gave the example that appetizing food aromas can induce the pre-prandial (or “cephalic phase”) secretion of insulin (via the vagus nerve stimulation of the parasympathetic nervous system) thereby causing a drop in blood glucose in a person who is in a fasted state and experiencing no hunger up until the point of smelling the appetizing aromas. Ivan Pavlov was once of the first to study this phenomenon. A good recent reference on this insulin-mediated hunger physiology is Karen Teff, “Physiological Effeccts of Flavour Perception”, Trends in Food Science and Technology, December 1996: http://gettingstronger.org/wp-content/uploads/2010/03/Teff-Flavour-Perception-1996.pdf

It is certainly true that other hormones, enzymes, and neuropeptides besides insulin play a role in the circuitry of hunger generation. For example, leptin is associated with time-dependent hunger regulation (though it appears leptin cannot play the role that insulin does in the sensory activation of hunger). Despite the complexity, I don’t think it can be denied that insulin is a major player in driving hunger, in many situations. This has been established, for example, by studies in which the vagus nerve is severed, cutting off the cephalic phase response, and thereby suppressing both insulin secretion and hunger. Sham feeding studies and intravenous feeding studies likewise provide strong evidence for the flavor/aroma-insulin-hunger connection.

So my point is a modest one: I do not deny that insulin can suppress appetite, but I think it is at the same time true that — under different circumstances — it can make you hungry. I think those other circumstances (sensory stimulation in the fasted state) are everyday occurrences for most people. And I think people with higher basal insulin levels and more active insulin responses are more prone to cravings induced by sensory stimulation, particularly in the fasted state. I know that my own cravings diminished significantly once I learned how to decondition my response to the sensory cues of appetizing food. How else can you explain this? What else besides insulin could cause the appetite to increase (or to stay quiet after being conditioned to do so) in these situations?

James comes close to acknowledging the role that insulin plays in stoking hunger. In resonse to my example, he states: “This is because insulin administration, in the absence of calories, causes hypoglycemia, which then induces hunger. So it is the hypoglycemia that causes the hunger, not the insulin.”

That’s an odd logic: If A causes B, which in turn causes C, should one conclude that it is not at all A, but rather only B, which causes C? While it is true that low blood sugar is a more proximate cause of hunger, that does not diminish the importance of causes earlier in the chain. I would argue that insulin plays a key causal role because it not only shunts glucose out of the bloodstream in response to sensory stimuli — it also inhibits fatty acid mobilization and counteracts adrenaline. In short, insulin acts on multiple pathways that lead to an increase in hunger and loss of satiety. Of course, further upstream of insulin are the psychological and sensory stimuli that induce the insulin. So there is no single “cause” of hunger. All I’m saying is that insulin plays a key role as a positive agent in the pathway that initiates hunger in many situations. Based on the studies James cites, I have no doubt that insulin can also play a hunger suppressing role in certain other situations, though I;m interested in which specific physiologically realistic situations these would be. Perhaps elevated insulin, after the passage of time, helps induce satiety towards the end of a meal. This would not be the first example of a cause having opposite effects under different circumstances.

In short, I do not think it is fair to label as “a myth” the observation that insulin can make you hungry.

In his above statement, James is the one taking a rather black-and-white position here. He flat out denies that insulin can make you hungry, calling it a “myth”. According to the statement above, insulin can ONLY suppress appetite.

This is a strawman representation of my position. First, nowhere have I stated that insulin can only suppress appetite, and my “myth/fact” statement does not imply a false dichotomy because my entire article is about how insulin operates under physiological conditions. The injection of insulin in a fasted state is not a relevant physiological condition. It has no relevance to how insulin operates in a fed state.

Now I am not denying that insulin might be able to have an inhibitory or suppressive effect on appetite. Based upon the experiments James cites, it appears that insulin can in fact suppress appetite when administered directly to certain regions of the brain, at certain doses, in certain situatioins.

Under all physiologically relevant conditions, the evidence indicates that insulin acutely inhibits appetite. There are a number of lines of evidence that indicates that this is true:

1. Numerous studies have shown that central insulin administration will inhibit food intake, at both high and low doses, in both animals and humans:

Even from an evolutionary standpoint, what you are trying to argue (insulin increasing hunger) does not make sense. Elevated insulin represents a fed state. The idea that a hormone that reflects a fed state will cause hunger under physiological conditions is not a logical conclusion.

The bottom line is that both experimental and observational studies show that insulin acutely suppressess appetite under physiological conditions in vivo. Your example of insulin injection in a fasted state has no relevance to real life.

I gave the example that appetizing food aromas can induce the pre-prandial (or “cephalic phase”) secretion of insulin (via the vagus nerve stimulation of the parasympathetic nervous system) thereby causing a drop in blood glucose in a person who is in a fasted state and experiencing no hunger up until the point of smelling the appetizing aromas.

Your hypothesis that cephalic phase insulin secretion increases hunger is not supported by the majority of the scientific data. In fact, numerous lines of evidence point against your hypothesis:

2. Similar to #1, appetitizing food creates powerful hedonic responses that are known to override natural physiological regulation of appetite. As palatable food is also associated with more robust cephalic phase responses, the increased cephalic phase responses may be more a psychological consequence of increased appetite, rather than a cause of people’s tendencies to overeat platable food. This is not to mention other factors of palatable food that disrupt natural appetite regulation mechanisms (such as high energy density)

6. There is no correlation between the cephalic phase insulin response and changes in blood glucose. In fact, two subjects in this study had strong cephalic phase insulin responses, yet no change in blood glucose. This indicates that changes in blood glucose during the cephalic phase are independent of insulin. This means that any drops in blood glucose during the cephalic phase are more likely due to direct neuronal regulation of hepatic glucose output rather than an effect of insulin.

This has been established, for example, by studies in which the vagus nerve is severed, cutting off the cephalic phase response, and thereby suppressing both insulin secretion and hunger

But when the vagus nerve is severed, many factors involved in the regulation of appetite are affected. You cannot use this data to support the idea that insulin increases hunger.

And I think people with higher basal insulin levels and more active insulin responses are more prone to cravings induced by sensory stimulation,

But again you are committing the cum hoc, ergo propter hoc fallacy here. People with high basal insulin levels are typically insulin resistant, and it is known that insulin resistance in the brain increases appetite (similar to how knocking out insulin receptors in the brain causes hyperphagia). Also, the “more active insulin” responses are more of a consequence rather than a cause of the heightened cravings (as indicated in my previous post).

I know that my own cravings diminished significantly once I learned how to decondition my response to the sensory cues of appetizing food. How else can you explain this? What else besides insulin could cause the appetite to increase (or to stay quiet after being conditioned to do so) in these situations?

Lots of reasons….lower ghrelin response, diminished effect of the hedonic/rewarding nature of the food, etc.

I would argue that insulin plays a key causal role because it not only shunts glucose out of the bloodstream in response to sensory stimuli

As I pointed out in my previous post, there is no relationship between cephalic phase insulin secretion and cephalic changes in blood glucose. On top of that, insulin primarily regulates blood glucose through control of hepatic glucose output rather than stimulation of peripheral glucose uptake….which will be addressed in part 3 of my series.

First, let me say that I highly respect your willingness and ability to take on the conventional wisdom and present a new view on insulin. You have certainly challenged me to take a closer look at recent research in this area. And you are very patient and respectful in dealing with all my questions, concerns, and challenges. Nevertheless, I’m still not convinced, so I’d like to continue our discussion.

1. I’ll start with a point of agreement: I think we would both acknowledge that insulin resistance is the core problem behind obesisty, not insulin spikes. Insulin spikes, as long as they are intermittent and not sustained, are the normal response of a healthy metabolism to meals.

2. While I agree with you that insulin resistance leads to sustained elevated insulin levels, I think this is only half of the vicious circle: it is equally true that elevated insulin levels, if sustained without being allowed to fall, will cause insulin resistance, particularly when combined with a diet high in fructose, saturated fat, and certain other triggers. Thus, it is important to allow insulin levels to come down between meals, by cutting out snacks, allowing a food-free window between dinner and sleep, and excercising judiciously.

3. I don’t agree with your position that the scientific literature conclusively establishes no impact of cephalic phase insulin on glucose levels or hunger. When I looked more closely at the articles you referenced, many of them did not actually support your synopses of their conclusions. For example, Bruce et al. (in your point #5) states that the stongest of the stimuli presented (combined tease meals plus sweet taste) resulted in “a significant fall in blood glucose levels and a variable rise in serum insulin”…within five minutes of the food presentation when compared with control studies, with no change seen in free fatty acid or pancreatic polypeptide levels. The blood glucose fall correlated strongly… with a score of the subjective response to the food and taste.” That doesn’t sound like “no correlation” to me. Morricone et al. (#7) found minimal glucose response to water, lemon or saccharin (not surprising to me) but “the combined and separate sight and smell of a meal for 2 min led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation).” Again, I think it is disingenuous to summarize the complexity of all these articles as unambiguously denying any connection between food stimuli, a cephalic phase insulin response, and an associated reduction in blood glucose.

4. You argue that, from an evolutionary standpoint, the view that insulin leads to increasing hunger does not make sense: “Elevated insulin represents a fed state. The idea that a hormone that reflects a fed state will cause hunger under physiological conditions is not a logical conclusion.” But I don’t see a problem here. First, I agree that a moderate insulin response, sufficient only to “cover” a modest meal, will typically not cause hunger. However, there are at least three situations in which an insulin response will cause hunger: (1) the case of insulin “overshoot” in which insulin is secreted in excess of what is required, bring the glucose levels back not merely to basline, but below baseline. This is not atypical, but is often experienced when eating a large meal meal of sugary or high glycemic foods, resulting in a reactive “crash”; (2) the case of an insulin resistant individual who tend to overconsume because of an impaired ability to uptake glucose, again resulting in insulin overshoot, and a subsequent crash; and (3) the case of a hyperactive cephalic phase insulin response to aromas or appetite cues, which is in fact acknowledged in several of your references in at least some cases.

5. You do not really offer an credible alternative to my explanation of how aromas, flavors and other food cues can cause hunger. Positing a “diminished effect of the hedonic/rewarding nature of the food” begs the question: what is the biochemical mechanism of the hedonic reward sytem? The hormones ghrelin and leptin cannot explain spontaneous short term cue-triggered hunger, as these hormones are responsive to regularized meal timing rather than proximal meal cues. (See Teff: http://endo.endojournals.org/cgi/content/full/147/1/20) By constrast, according to the references cited in the Teff article, cephalic phase insulin has been shown to respond immediately, literally within minutes, to cues which are presented spontaneously. Thus, among these hormones, only insulin – and not ghrelin or leptin – has so far been shown to be capable of playing the role of a hormonal mediator between non-temporal appetite cues and hunger.

6. You are right that “when the vagus nerve is severed, many factors involved in the regulation of appetite are affected”, so such experiments cannot by themselves prove that insulin is the sole factor, or even one of the factors, responsible for inducing hunger. I agree that there may be additional factors. But certainly there is evidence that insulin is among these. (See Teff: http://gettingstronger.org/wp-content/uploads/2010/03/Teff-Flavour-Perception-1996.pdf). According to Teff, the cephalic phase response is indeed variable – it is stongest for hedonically preferred foods and flavors, and is strongest in “unrestrained” eaters as opposed to “restrained” eaters. So the variability itself gives insight into the role that preprandial insulin plays in hunger.

7. Finally, I do not deny that “central administration” (i.e. injecting insulin directly into the brain) can suppress appetite. But physiological insulin does not act on the brain alone. It acts first in the liver, bloodstream, muscle, and adipose tissues and its effect on circulating levels of glucose and fatty acids contributes to the “integrated” appetite response, at least in the situations I’ve suggested above. So the action of insulin on brain centers must be intergrated with other system effects. And it does make biological sense that an inhibitory effect on appetite would help to put the brakes on appetite as one enters the fed state (except in the case of overshoot or impaired insulin sensitivity, as discussed above).

In short, I acknowledge that insulin is only one of many effectors of hunger. For example, leptin plays a role in hunger in relation to fasting and body weight; ghrelin plays a role in hunger in relation to meal timing. But insulin also has its role. At a minimum, it has been implicated in hunger initated spontaneously and rapidly in response to food cues, such as aromas or tasty food. And it can also explain “rebound” hunger such as the return of hunger after eating high glycemic foods, and possibly also the well known “Chinese Restaurant Effect”, whereby hunger returns more quickly for certain foods.

I also think that the insulin response model is consistent with observations that obese, insulin-resistant individuals tend to experience greater hunger than lean, insulin-sensitive individuals. Which brings us back to the point of agreement, namely that insulin resistance is a greater problem than insulin spikes.

I think we would both acknowledge that insulin resistance is the core problem behind obesisty, not insulin spikes.

Even there, though, I would disagree with you somewhat. I don’t think there is any single core problem behind obesity; I am of the stance that obesity is caused by positive energy balance, which itself is caused by a huge number of factors operating simultaneously. I am also of the stance that the combination of factors that lead to obesity in one person are not the same combination that led to obesity in another person. Also, there is a subset of obese people who actually remain insulin sensitive, so insulin resistance cannot necessarily be the single core problem. There is also the issue of whether insulin resistance leads to obesity, or obesity leads to insulin resistance. There is data to indicate that both are true. So it actually all becomes quite complicated when you dig deeper.

it is equally true that elevated insulin levels, if sustained without being allowed to fall, will cause insulin resistance,

But unless someone is chronically feeding 24 hours a day (and thus would be overfeeding in the first place), insulin secretion is never sustained without being allowed to fall. This is not to mention the fact that you have to consider overall energy intake. Even if I did feed 24 hours a day, if I only slowly consume 100 calories per hour (and my energy requirements are 2400 calories per day), I will not become insulin resistant (ignoring the fact that sleep loss causes insulin resistance), because the amount of food is so small that the insulin secretion, while continuous, will be low.

Thus, it is important to allow insulin levels to come down between meals, by cutting out snacks, allowing a food-free window between dinner and sleep, and excercising judiciously.

But snacks or food-free windows do not matter over the context of a 24-hour period, if one remains in energy balance. In one study, there was no difference in the daily insulin AUC when 2 meals was compared to 12 meals. Another study showed similar results for AUC when a single meal was given, or the meal was divided into 5 equal portions over 5 hours. Other research has actually shown greater insulin levels with less frequent feeding (although this research used liquid diets, which may not necessarily apply to real food diets).

For example, Bruce et al. (in your point #5) states that the stongest of the stimuli presented (combined tease meals plus sweet taste) resulted in “a significant fall in blood glucose levels and a variable rise in serum insulin”…within five minutes of the food presentation when compared with control studies, with no change seen in free fatty acid or pancreatic polypeptide levels. The blood glucose fall correlated strongly… with a score of the subjective response to the food and taste.” That doesn’t sound like “no correlation” to me.

Please re-read what I stated about the Bruce paper. I stated:

There is no correlation between the cephalic phase insulin response and changes in blood glucose. In fact, two subjects in this study had strong cephalic phase insulin responses, yet no change in blood glucose. This indicates that changes in blood glucose during the cephalic phase are independent of insulin.

Now re-read what you stated:

The blood glucose fall correlated strongly… with a score of the subjective response to the food and taste.” That doesn’t sound like “no correlation” to me

Do you see the difference between your statement and mine? The blood glucose fall correlated with the subject’s subjective response to food and taste…not to the cephalic phase insulin response. This was even discussed by the authors of the paper…that the change in blood glucose was independent of changes in insulin. This (along with the other pieces of data I cited from other research) contradicts your assertion that the cephalic phase insulin response is responsible for inducing hunger by inducing a decrease in blood glucose. The insulin response in the Bruce paper did not cause the changes in blood glucose.

Morricone et al. (#7) found minimal glucose response to water, lemon or saccharin (not surprising to me) but “the combined and separate sight and smell of a meal for 2 min led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation).”

But as I stated earlier, you are committing the cum hoc, ergo propter hoc fallacy. Just because the two correlate, does not mean one causes the other. And it is clear from the Bruce paper (along with the other data I cited) that it is merely a correlational relationship and not a causal one.

“The fact is that insulin is not this terrible, fat-producing hormone that must be kept as low as possible. It is an important hormone for appetite and blood sugar regulation. In fact, if you truly wanted to keep insulin as low as possible, then you wouldn’t eat a high protein diet…you would eat a low protein, low carbohydrate, high fat diet. However, I don’t see anybody recommending that.”

Actually, I’d say this is the most recommended type of diet I’ve seen in the paleo world:

I’ve waited a few weeks for the rest of your response, but it looks like you’ve been busy on other topics. So I’m going to follow-up to your most recent reply:

First a caveat: I notice that you rely quite a bit on abstracts from PubMed, since you link to them in your posts. I assume that you have ready access to the entire studies. However, since most of us don’t have free access and cannot evaluate the full studies and data firsthand, it is hard provide a fair judgment of your interpretations of the data, beyond what is apparent in the abstracts alone. With that caveat, I would like to address your comments:

Well, of course the first law of thermodynamics is true: nobody can plausibly deny that a positive energy balance leads to weight gain. But the more burning question is what drives people to overeat (relative to energy expenditure) in the first place. Overeating is typically associated with a stronger appetite. So why do some people have a much stronger appetite? One likely culprit is the high basal insulin level (which can result from a high carbohydrate diet, or even too much protein) that is often associated with insulin resistance. (I’m not talking about insulin spikes or AUC, but high basal or fasting insulin). Insulin resistant (IR) individuals eat more than their insulin sensitive (IS) counterparts, in part because it takes longer for the insulin to kick in and transport glucose into the cells, satisfying their hunger. Thus, IR individuals eat more because of this delayed response, which can also lead to “overshoot” in insulin, and rebound hunger. The high basal insulin levels make it harder to access stored fat and glycogen stores, making IR individuals further prone to hunger from any dip in blood glucose or fatty acids during the day. It’s a vicious circle, really.

You’ve so far offered no alternative theory as to the biochemical basis of an excessive appetite, or an appetite that is easily stimulated by short-term food cues (aromas, flavors, visual cues). Ghrelin and leptin can explain hunger associated with meal timing, but not cue-triggered appetite. Citing “hedonic” factors begs the question of the biochemical basis for the psychological response. On the other hand, pre-prandial insulin secretion, mediated by the vagus nerve (see Teff article I cited above) can explain this.

Agreed.

So you and I agree that some causal relations can be circular. The IR-obesity link is one such “viscious circle” that often get progressively worse over time. I would be interested to know more about the subset of obese people who remain insulin sensitive. Is there any research regarding (a) what percentage of the obese are insulin sensitive; (b) in what other respects, biochemically, behaviorally or genetically, they differ?

I don’t think you have to be eating 24 hours a day to have an elevated insulin level. I reduced my fasting insulin level from 15 µU/mL(borderline IR) down to 4µU/mL (IS) by using a low carb diet in combination with intermittent fasting. Even when borderline IR, however, I was not eating 24 hours a day, yet my basal insulin was elevated. If you have insulin resistance, even if you allow many hours between meals, your insulin level never really gets very low, which makes it much harder to burn fat and glycogen. With my lower insulin levels, I now get hungry far less often. Please explain that, if it is not due to lower basal insulin and improved IS.

Your scenario of slowly consuming 100 calories per hour doesn’t prove anything; nor do the studies showing reduced AUC with smaller, more frequent meals. While I agree such a diet will avoid insulin spikes and keeps the AUC insulin low, and may avoid IR, it still might not allow basal insulin levels to drop sufficiently low to allow for efficient fat burning and weight loss (beyond perhaps some initial loss if one is overweight) without a compensating increase in exercise or other physical activity. I never argued that insulin spikes or high AUC were a problem. My main point is that hunger is driven by insulin in two respects: (a) a high basal insulin makes one more prone to hunger, because the elevated insulin makes it much harder to access stored fats and glycogen fuels; and (b) hunger is often conditioned to respond to short-term food cues in a Pavlovian manner, and there is evidence that this Pavlovian response involves pre-prandial secretion of insulin. (See Teff article).

You addressed only the second half of what I excerpted from the Bruce paper. Read again the sentences of mine that you did not comment on:

Bruce cited a correlation between “a signficiant fall in blood glucose levels” and “a variable rise in serum insulin” within five minutes after the food cues, and with no other changes in pancreatic hormones or blood fats. So the correlation is in fact mentioned in the Bruce paper, despite your denial of it. Further, the fact both the glucose drop and insulin rise occur within 5 minutes of the food presentation is highly significant, since this can be explained by the speed of a cephalic phase resonse, but not by a post-prandial insulin reponse, and not by a grhelin or leptin response. How do you otherwise explain the rapidity of this response?

Obviously, correlation does not prove causation. But that is not the point. You argued that there was no correlation reported…and there was. To provide causation would require additional studies, and I’m happy to research those for you. But you likewise have not proved that insulin is not the cause of hunger in the context of normal digestion, and most of the studies you cite are also only correlational. Since you are the one who is claiming that it is a “myth” that insulin causes hunger, I think the burden of proof is on you to provide positive evidence that this is a myth. Studies of “central administation” of insulin injected into the brain won’t suffice, because such an injection does not represent the normal context in which insulin is first secreted in digestion and acts on blood glucose before it acts in the brain. Since insulin can have different actions on different tissues, you cannot just isolate one step in the process, out of the normal physiological context, and draw strong conclusions from that. The fact that insulin may inhibit hunger when it eventually reaches the brain is only one piece of a larger puzzle, and certainly not the whole story.

On the other hand, measurements of pre-prandial insulin secreted due to food presentation (without ingesting the food), are not artificial ‘injection” studies, but represent a “normal” context that happens to people every day. (We often get hungry when smelling or seeing delicious food, before eating it). So the studies I cite are more contextually realistic than the central administration studies you cite.

You have also still not addressed my point, in response to your comment above, that if insulin causes hunger by first causing a drop in glucose, it can still be said to be a cause of hunger. Proximate causes are not the only types of cause; some causes are mediated. If cause A (insulin) causes effect B (hypoglycemia) and B causes effect C (hunger), A is stlll a cause of C. You, as an advocate of rigorous logic, should admit this.

In short, you have still not made your case that it is a “myth” that insulin causes hunger, and you have not provided a plausible biochemical alternative to explain how hunger and appetite can arise spontaneously in response to short term food cues, that operate on the scale of minutes. You have also not explained why obese, insulin resistant individuals typically have a more hyperactive, easily triggered hunger response, which also takes longer to satisfy. The insulin response theory provides a plausible explanation for all of these facts, and I’ll stick with this theory until you provide a plausible alternative.

I see that I did not correctly use the blockquote editing feature. Since I could not preview or edit my comment syntax, I wasn’t sure how it worked. I see it resulted in incorrect formatting. Can you please sort it out for me?

I’ve waited a few weeks for the rest of your response, but it looks like you’ve been busy on other topics. So I’m going to follow-up to your most recent reply:

First a caveat: I notice that you rely quite a bit on study abstracts from PubMed, since you link to them in your posts. I assume that you have ready access to the entire studies. However, since most of us don’t have free access and cannot evaluate the full studies and data firsthand, it is hard provide a fair judgment of your interpretations of the data, beyond what is apparent in the abstracts alone. With that caveat, I would like to address your comments:

I am of the stance that obesity is caused by positive energy balance, which itself is caused by a huge number of factors operating simultaneously.

Well of course the first law of thermodynamics is true; nobody can plausibly deny that a positive energy balance leads to weight gain. But the more burning question is what drives people to overeat (relative to energy expenditure) in the first place. Overeating is typically associated with a stronger appetite. So why do some people have a much stronger appetite? One likely culprit is the high basal insulin level (which can result from a high carbohydrate diet, or even too much protein) that is often associated with insulin resistance. (I’m not talking about insulin spikes or AUC, but high basal or fasting insulin). Insulin resistant (IR) individuals eat more than their insulin sensitive (IS) counterparts, in part because it takes longer for the insulin to kick in and transport glucose into the cells, satisfying their hunger. Thus, IR eat more because of this delay, which can also lead to “overshoot” in insulin, and rebound hunger. The high basal insulin levels make it harder to access stored fat and glycogen stores, making IR individuals further prone to hunger from any dip in blood glucose or fatty acids during the day. It’s a vicious circle, really.

You’ve so far offered no alternative theory as to the biochemical basis of an excessive appetite, or an appetite that is easily stimulated by short-term food cues (aromas, flavors, visual cues). Ghrelin and leptin can explain hunger associated with meal timing, but not cue-triggered appetite. Preprandiall insulin secretion, mediated by the vagus nerve (see Teff article I cited above) can explain this.

I am also of the stance that the combination of factors that lead to obesity in one person are not the same combination that led to obesity in another person.

Agreed.

Also, there is a subset of obese people who actually remain insulin sensitive, so insulin resistance cannot necessarily be the single core problem. There is also the issue of whether insulin resistance leads to obesity, or obesity leads to insulin resistance. There is data to indicate that both are true.

So you and I agree that some causal relations can be circular. The IR-obesity link is one such “viscious circle” that often get progressively worse over time. I would be interested to know more about the subset of obese who remain insulin sensitive. Is there any research regarding (a) what percentage of the obese are insulin sensitive; (b) in what other respects, biochemically, behaviorally or genetically, they differ?

But unless someone is chronically feeding 24 hours a day (and thus would be overfeeding in the first place), insulin secretion is never sustained without being allowed to fall. This is not to mention the fact that you have to consider overall energy intake. Even if I did feed 24 hours a day, if I only slowly consume 100 calories per hour (and my energy requirements are 2400 calories per day), I will not become insulin resistant (ignoring the fact that sleep loss causes insulin resistance), because the amount of food is so small that the insulin secretion, while continuous, will be low….But snacks or food-free windows do not matter over the context of a 24-hour period, if one remains in energy balance. In one study, there was no difference in the daily insulin AUC when 2 meals was compared to 12 meals. Another study showed similar results for AUC when a single meal was given, or the meal was divided into 5 equal portions over 5 hours. Other research has actually shown greater insulin levels with less frequent feeding (although this research used liquid diets, which may not necessarily apply to real food diets).

I don’t think you have to be eating 24 hours a day to have an elevated insulin level. I reduced my fasting insulin level from 15 µU/mL(borderline IR) down to 4µU/mL (IS) by using a low carb diet in combination with intermittent fasting. Even when borderline IR, however, I was not eating 24 hours a day, yet my basal insulin was elevated. If you have insulin resistance, even if you allow many hours between meals, your insulin level never really gets very low, which makes it much harder to burn fat and glycogen. With my lower insulin levels, I know I get hungry far less often. Please explain that.

Your scenario of slowly consuming 100 calories per hour doesn’t prove anything; nor do the studies showing reduced AUC with smaller, more frequent meals. While I agree such a diet will avoid insulin spikes and keeps the AUC insulin low, and may avoid IR, it may still not allow basal insulin levels to drop sufficiently low to allow for efficient fat burning and weight loss (beyond perhaps some initial loss if one is overweight) without a compensating increase in exercise or other physical activity. I never argued that insulin spikes or high AUC were a problem. My main point is that hunger is driven by insulin in two respects: (a) a high basal insulin makes one more prone to hunger, because the elevated insulin makes it much harder to access stored fats and glycogen fuels; and (b) hunger is often conditioned to respond to short-term food cues in a Pavlovian manner, and there is evidence that this Pavlovian response involves pre-prandial secretion of insulin. (See Teff article).

There is no correlation between the cephalic phase insulin response and changes in blood glucose…Do you see the difference between your statement and mine? The blood glucose fall correlated with the subject’s subjective response to food and taste…not to the cephalic phase insulin response. This was even discussed by the authors of the paper…that the change in blood glucose was independent of changes in insulin. This (along with the other pieces of data I cited from other research) contradicts your assertion that the cephalic phase insulin response is responsible for inducing hunger by inducing a decrease in blood glucose. The insulin response in the Bruce paper did not cause the changes in blood glucose.

You addressed only the second half of what I excerpted from the Bruce paper. Read again the sentences you did not comment on:

“Bruce et al. (in your point #5) states that the strongest of the stimuli presented (combined tease meals plus sweet taste) resulted in “a significant fall in blood glucose levels and a variable rise in serum insulin”…within five minutes of the food presentation when compared with control studies, with no change seen in free fatty acid or pancreatic polypeptide levels.

Bruce cited a correlation between “a signficiant fall in blood glucose levels” and “a variable rise in serum insulin” within five minutes after the food cues, and with no other changes in pancreatic hormones or blood fats. So the correlation is in fact mentioned in the Bruce paper, despite your denial of it. Further, the fact both the glucose drop and insulin rise occur within 5 minutes of the food presentation is highly significant, since this can be explained by the speed of a cephalic phase resonse, but not by a post-prandial insulin reponse, and not by a grhelin or leptin response. How do you otherwise explain the rapidity of this reponse?

Obviously, correlation does not prove causation. But that is not the point. You argued that there was no correlation reported…and there was. To provide causation would require additional studies, and I’m happy to research those for you. But you likewise have not proved that insulin is not the cause of hunger in the context of normal digestion, and most of the studies you cite are also only correlational. Since you are the one who is claiming that it is a “myth” that insulin causes hunger, I think the burden of proof is on you to provide positive evidence that this is a myth. Studies of “central administation” of insulin injected into the brain won’t suffice, because such an injection does not represent the normal context in which insulin is first secreted in digestion and acts on blood glucose before it acts in the brain. Since insulin can have different actions on different tissues, you cannot just isolate one step in the process, out of the normal physiological context, and draw strong conclusions from that. The fact that insulin may inhibit hunger when it eventually reaches the brain is only one piece of a larger puzzle, and certainly not the whole story.

On the other hand, measurements of pre-prandial insulin secreted due to food presentation (without ingesting the food), are not artificial ‘injection” studies, but represent a “normal” context that happens to people every day. So the studies I cite are more contextually realistic.

This is because insulin administration, in the absence of calories, causes hypoglycemia, which then induces hunger. So it is the hypoglycemia that causes the hunger, not the insulin.

You have also still not addressed my point, in response to your comment above, that if insulin causes hunger by first causing a drop in glucose, it can still be said to be a cause of hunger. Proximate causes are not the only types of cause. If A (insulin) causes B (hypoglycemia) and B causes C (hunger), A is stlll a cause of C. You, as an advocate of rigorous logic, should admit this.
In short, you have still not made your case that it is a “myth” that insulin causes hunger, and you have not provided a plausible biochemical alternative to explain how hunger and appetite can arise spontaneously in response to short term food cues, that operate on the scale of minutes. You have also not explained why obese, insulin resistant individuals typically have a more hyperactive, easily triggered hunger response, which also takes longer to satisfy. The insulin response theory provides a plausible explanation for all of these facts, and I’ll stick with this theory until you provide a plausible alternative.

Nice work. You hit on many of the same themes that I have been pointing out to low-carbers over the past 2 years, after I myself and many others developed health problems following all different kinds of version of a low-carb diet, including the uber low-insulin version of high-fat, low-carb, low-protein – which is a great way to develop nutritional deficiencies if you ask me. My tooth pain was out of this world.

You are also welcome to borrow my “Insulin Bin Laden” catch phrase to describe how low-carb “scientists” have “butchered” any signs of a smart, fair, balanced, and intelligent viewpoint about carbohydrates, insulin, weight loss, longevity, and so forth.

And I think you are on to the real answers with the concept of calorie density, and also absorption rate, and how it impacts our ratio of appetite to metabolism (the higher the ratio, the fatter we get).

What I love is that during overfeeding, the lower your insulin, the more fat and less muscle you store out of the caloric excess. Classic.

5000 kCal of sugar can easily be consumed in the form of a king size fast-food meal and lots of soda. That’s where the problem for a lot of the obese lies. For the rest I understand your point. Of course we need insulin, ask it a diabetic type I.

In carefully re-reading your post, I realized I overlooked some significant unproven claims based on improper extrapolation from limited evidence and nonsequitors in logic. Let’s review some of your key contentions:

(1) I mentioned earlier how insulin will suppress lipolysis. Well, some people think that glucagon increases lipolysis to cancel this out. Research using modern techniques has shown that glucagon does not increase lipolysis in humans. Other research using the same techniques has shown similar results. I will also note that this research failed to find any lipolytic effect in vitro.

But the main, indisputed function of glucagon is not lipolysis, but the rather the hydrolysis of glycogen to glucose (gluconeogensis). That alone is sufficient to at least partially counteract the impact of protein consumption on energy storage. And that will also tend to counteract hunger due to hypoglycemia. But even your contention that glucagon does not increase lipolysis is not proven. In the study you cite by Gravholt et al, the conditions are highly contrived: where glucagon is administered with continuous insulin and growth hormone infusion, and glycerol was taken to be the sole indicator of lipolysis. (But glycerol can derive from sources other than stored fat). This situation is so contrived and artificial, and begs so many questions that it can by no means be regarded as a definitive indicator of how glucagon works during actual physiological ingestion of protein.

(2) It should be remembered why glucagon is released in response to protein in the first place. Since protein stimulates insulin secretion, it would cause a rapid drop in blood glucose if no carbohydrate is consumed with the protein. Glucagon prevents this rapid drop in blood sugar by stimulating the liver to produce glucose.

This is precisely the reason why protein is more satiating than carbohydrate!! The fact that protein (unlike carbohydrate) induces glucagon, leading to gluconeogenesis, means that blood glucose is better balanced after protein ingestion vs. carbohydrate ingenstion—a strong indicator that protein is more satiating than carbohydrate, since it does not lead to a similar swing in blood glucose.

(3) Now, you may be wondering why refined carbohydrates can be a problem. Many people think it’s due to the rapid spikes in insulin. However, it’s obviously not the insulin, because protein can cause rapid spikes in insulin as well. One problem with refined carbohydrate is a problem of energy density. With refined carbohydrate, it is easier to pack a lot of calories into a small package. Not only that, but foods with high energy density are often not as satiating as foods with low energy density. In fact, when it comes to high-carbohydrate foods, energy density is a strong predictor of a food’s ability to create satiety (i.e., low-energy density foods create more satiety). There are other issues with refined carbohydrate as well that are beyond the scope of this article.

But as you just admitted, protein, unlike carbohydrate, induces gluconeogenesis via stimulation of glucagon. So protein, unlike carbohydrate, balances the glucose-storing effect of insulin with the glucose-releasing effect of glucagon. Furthermore, “energy density” cannot be the sole explanation for satiety. For example, pure fat is more energy dense than carbohydrate. Yet high fat (in the absence of carbohydrate) is highly satiating, as is a high protein / low carbohydrate diet. High fat and/or high protein ketogenic diets can be incredibly satiating. This is not only something you can experience directly (try drinking some heavy whipping cream diluted in water versus drinking a sugary soda). This is also attested to by numerous studies:http://www.ajcn.org/cgi/content/abstract/65/5/1410http://www.ajcn.org/cgi/content/abstract/87/1/44http://www.annals.org/content/142/6/403.abstract

(By the way, many studies of so-called “high fat” diets are compromised by including significant carbohydrate together with the fat.. a valid study should exclude carbohydrate).

You just cannot oversimplify by focusing on “nutrient density” as the sole driver of appetite. The study you cite on energy density compares only different types of bread! So while whole wheat bread is less energy dense and more satiating than white bread, that relationship cannot be extrapolated to the relative satiating effects of other macronutients such as protein and fat from a study that is only about bread!

I think it is important not to extrapolate beyond the limits of a very specific study to making broad general claims beyond what the evidence shows. You cite study after study where I think you draw generalized conculsions that go well beyond the specific conditions of the study.

One more point about insulin and hunger: I’ve searched the literature and am coming upon many studies along the lines you are citing, arguing that insulin does not increase hunger or eating behavior. Here is yet another study which makes this point very strongly:http://ajpregu.physiology.org/cgi/content/full/274/3/R596

But what I just noticed is that these studies (and others like it) administer the insulin under euglycemic conditions. In other words, they administer the insulin while injecting glucose intravenously so as to maintain a steady glucose concentration. But then its no wonder that hunger and eating behavior is suppressed! I’m not aware of anyone who claims that elevated insulin per se causes hunger. It is only the effect of insulin in causing a drop in glucose (while inhibiting gluconeogenesis and lipolysis) that results in an uptick in appetite. And this is even more pronounced in cases of insulin overshoot, which can happen with a high glycemic index (or high glycemic load) meal, or less commonly, with a very high protein meal.

To say that insulin does not by itself cause hunger, by citing a study where the glucose concentration is maintained by continuous replacement, is a bit like saying that a drain is ineffective in emptying a bath tub, by demonstrating that the tub doesn’t drain as long as you are pumping fresh water into it. Or that a lit match cannot cause paper to burn, by showing that no burning takes place when we blow the oxygen away with a stream of carbon dioxide. Any “cause” can be counteracted.

The fact is that elevated insulin not only makes hunger more likely (as long as you don’t refeed), because it not only depletes blood glucose faster; it also inhibits the release of stored glucose from glycogen (and fatty acids from adipose tissue) which would otherwise resupply the fuel needed to stave off hunger. The fact that insulin, administered peripherally or naturally secreted does this by virtue of causing hypoglycermia (the proximate cause) does not make insulin any less responsible for this action. Further, the fact that insulin administered centrally inhibits appetite shows at best that this inhibitory effect (which occurs later in time than the initial effect in the bloodstream, liver, muscle and fat tissues) will eventually balance out the initial hunger. But that is not to deny the initial effect on hunger.

Todd

(P.S. If you get the chance, please delete my earlier note that has the incorrectly formatted block quotes. Thanks)

Krieger writes, “If you truly wanted to keep insulin as low as possible, then you wouldn’t eat a high protein diet…you would eat a low protein, low carbohydrate, high fat diet. However, I don’t see anybody recommending that.”

Krieger should read some of the low-carb sites, as yes, low-carb, low (or modest) protein, and high fat IS what’s recommended.

Krieger also writes, “The fact is that insulin is not this terrible, fat-producing hormone that must be kept as low as possible. It is an important hormone for appetite and blood sugar regulation. ”

Here is yet one more study, Campfield and Smith (1990), that very clearly demonstrates the causal chain from insulin to transient hypoglycemia to hunger: http://tinyurl.com/2edhpbb

Here are the key conclusions:

The aim of these studies was to determine if meal requests and changes in hunger ratings in humans were related to spontaneous changes in blood glucose concentration. In our first study, 18 healthy subjects were acutely isolated from food and time cues. Blood glucose was continuously monitored online and visual analog ratings of hunger were obtained following an overnight fast…. Each subject was studied twice: either insulin or saline was infused while hunger ratings were obtained. Preliminary results in five subjects indicate that hunger ratings increased after insulin-induced transient declines in blood glucose. No change in hunger ratings occurred when blood glucose concentration was stable.

How do you square the insulin induced hunger in this study with your claim that insulin does not increase hunger, but inhibits it? My explanation is that the hypothalamic hunger centers INTEGRATE many signals, including energy metabolites (glucose, fatty acids, ketones), hormones and signalling peptides (insulin, glucagon, epinehrine, ghrelin, PYY, CCK, etc.). Insulin initially causes hunger via causing hypoglycemia, but may eventually attenuate or inhibit hunger in the brain ONCE THE OTHER SIGNALS WEAKEN. But net, insulin stimulates hunger in full physiological context, where glucose levels do in fact fluctuate. This is different than the highly artificial situations contrived in other studies you site, wherein glucose is continuously infused to counteract any hunger-inducing effect of insulin. It is not surprising in those situations that the single variable effect of insulin may inhibit hunger.

[…] Insulin: An Undeserved Bad Reputation, Part 1 Insulin has gotten a bad reputation it doesn’t deserve. It is an important hormone for regulating appetite and blood sugar. There are many misconceptions regarding insulin that are clarified in this article. […]